We propose to study the modification of responses to radiation treatments by a group fo semisynthetic DNA non-binding derivatives (DNBD) of adriamycin, currently undergoing clinical evaluation. Because of the nature of DNA macromolecular damage caused by ionizing irradiation and by DNB anthracyclines, it is expected that interaction of the two modalities occurs. This seems to be confirmed by presented pilot studies. Since numerous clinical situations can be anticipated where radiation and the new anthracyclines will be considered either as combination or sequential treatment, we plan to investigate their interaction in mouse tumor lines of a mammary carcinoma and a lymphoma. Cytotoxicity will be assayed by plating techniques, cell-cycle effects by flow cytometry, molecular effects by DNA alkaline elution and by the techniques investigating the specificity of DNA cleavage, and pharmacokinetics by HPLC. We plan the following studies: 1) Pharmacokinetics of DNB derivatives in tumors and in two normal critical tissues, the bone marrow and intestines; 2) Establishing whether the combination of irradiation and DNB derivatives results in potentiation, additivity or inhibition of effects in tumors; 3) Characteriation of the interaction at DNA macromolecular level; 4) Interaction of both modalities in hypoxic and euoxic tumor cells; 5) Cell-cycle effects, using tumor cells synchronized by elutriation; and 6) Evaluation of cytotoxicity of both modalities against the bone marrow and intestines. Scientific disciplines: Experimental Oncology; Cell Kinetics; Biochemistry; Pharmacology.